文章摘要
徐 静,周 鑫,张 慧,周建伟.血清白蛋白水平可预测UGT1A1基因分型伊立替康化疗的不良反应[J].南京医科大学学报,2017,(12):1567~1571
血清白蛋白水平可预测UGT1A1基因分型伊立替康化疗的不良反应
The serum albumin as a biomarker to predict toxic effects of UGT1A1 genotyping directed irinotecan chemotherapy
投稿时间:2017-06-17  
DOI:10.7655/NYDXBNS20171206
中文关键词: UGT1A1  基因型  白蛋白  伊立替康  不良反应
英文关键词: UGT1A1  genotype  albumin  irinotecan  toxic effects
基金项目:江苏省六大人才高峰(2015-WSW-022)
作者单位
徐 静 南京医科大学公共卫生学院江苏 南京 211166南京医科大学第一附属医院肿瘤科,江苏 南京 210029 
周 鑫 南京医科大学第一附属医院肿瘤科,江苏 南京 210029 
张 慧 肝脏外科江苏 南京 210029 
周建伟 南京医科大学公共卫生学院江苏 南京 211166 
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中文摘要:
      目的: 探讨按UGT1A1基因多态性分型指导伊立替康治疗肿瘤用药后部分患者的不良反应原因,寻找新的辅助性分子分型标志物。方法:收集本院收治的269例含伊立替康化疗方案治疗的恶性肿瘤患者。在治疗前采用PCR毛细管电泳法分析每例患者UGT1A1的基因多态性,用常规试剂盒检测血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、血清肌酐及血清白蛋白等肝肾功能水平,按现有NCCN指南建议的基因分型标准确定伊立替康化疗方案,观察患者接受分型治疗后不良反应减轻程度,采用Wilcoxon秩和检验比较患者的不良反应与多个肝肾功能指标之间的可能关系。结果:根据UGT1A1*28基因型实施剂量差异化治疗后的269例中均获得预期效果,其中238例未观察到明显不良反应,但31例(11.5%)出现白细胞计数减少和腹泻等为特征的较严重的不良反应。发生严重的不良反应组治疗前血清白蛋白水平(34.9±3.0 g/L)显著低于无不良反应组(41.4±3.5) g/L (P <0.05)。ROC分析提示白蛋白水平具有良好的可预测伊立替康不良反应的能力(曲线下面积达到0.926 6)。两组之间AST水平差异虽具有统计学意义(OR=0.98, 95%CI:0.97~1.00,P<0.05),但其ROC曲线下面积仅为0.679 7,预测价值一般。肿瘤的病理类型、性别、年龄、UGT1A1*28、UGT1A1*6基因型以及其他肝肾功能指标与不良反应的发生无明显统计学相关性(P>0.05)。结论:肿瘤患者治疗前的血清白蛋白水平较低与伊立替康导致的不良反应有密切关系,血清白蛋白水平可作为预测伊立替康产生不良反应的生物标志物。
英文摘要:
      Objective: To explore the new biomarkers for predicting the side effects of UGT1A1 genotyping directed chemotherapy. Methods: A total of 269 patients were enrolled in the present study. Each patient was determined polymorphism of UGT1A1 gene for genotyping. Serum biochemical markers including alanine aminotransferase (ALT), aspartate aminotransferase(AST), creatinine (Scr) and plasma albumin (ALB) were also analyzed routinely prior to treatment. According to the NCCN(2017V1) guidelines, the differential doses of irinotecan were set according to the genotyping of the patients. The relationships between the side effects and blood biochemical markers were analyzed by Wilcoxon's rank-sum test. Results: The overall toxic effects in patients was significantly reduced under the genotyping directed irinotecan treatment in patients. However, 31 cases (11.5%) were found with severe irinotecan specific toxic effects. Furher analysis indicated that serum AST was associated with toxic effects of irinotecan but with lower predicted value (OR=0.98, 95% confidence interval: 0.97 ~ 1.00, P<0.05; Area under the ROC curve, AUC was 0.6797). Interestingly, low ALB level before treatment was indicated significant correlation with irinotecan induced toxic effects (OR=1.51, 95% confidence interval: 1.34 ~ 1.71, P<0.05). ROC analysis showed that the area under the curve of albumin was reached up to 0.9266. However, pathological type of tumor, gender, age, and other serum biomarker were without obvious correlations with irinotecan induced toxic effects. Conclusion: Low ALB before treatment was significantly associated with irinotecan induced toxic effects in patients and it might be a potential predicting biomarker for UGT1A1 genotyping directed chemotherapy in clinic.
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